J. Phys. Chem. C 2010, 114, 11009–11017
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Advances in Coating Chemistry in Deriving Soluble Functional Nanoparticle SK Basiruddin, Arindam Saha, Narayan Pradhan, and Nikhil R. Jana* Centre for AdVanced Materials, Indian Association for the CultiVation of Science, Kolkata-700032, India ReceiVed: January 28, 2010; ReVised Manuscript ReceiVed: April 23, 2010
Nanoparticle-based probes are emerging as alternatives to molecular probes with several advantages. A variety of water-soluble functional nanoparticles and nanobioconjugates need to be prepared and tested for this research. Development of appropriate coating chemistries is the key in deriving such functional nanoparticles. Herein we summarize different coating approaches those we have developed and compared them in the context of currently available coating methods, for the synthesis of soluble functional nanoparticles. We have focused on conventional ligand exchange, interdigited bilayer strategy, silica coating, polyacrylate coating, and imidazole based polymer coating and found that cross-linked coating, specifically by polyacrylate, provides a superior colloidal stability of nanoparticles. The robust coating provides the opportunity to explore various conjugation chemistries involving nanoparticle and to derive different soluble nanobioconjugates. A library of functional nanoprobes with hydrodynamic diameters of 10-100 nm are synthesized with these coating approaches which are composed of different nanoparticles (e.g., metal, metal oxide, or semiconductor) and affinity molecules (e.g., oligonucleotide, peptide, antibody, vitamins, etc.) and can be explored for cellular and subcellular imaging and ultrasensitive biosensing applications. 1. Introduction Semiconductor, noble metal and metal oxide nanoparticles of 1-100 nm size are new class of materials with unique sizedependent properties.1-4 Some of them have stable, brighter, and tunable optical properties compared to conventional molecular probes that prompted researchers to use them in various imaging and sensing applications in biomedical science.5-10 It is hoped that these applications would lead to variety of essential tools in medical diagnostics and for understanding disease pathology at the molecular length scale.11-14 Thus a variety of functional nanomaterials should be prepared, and their application potentials need to be tested. However, this is challenging interdisciplinary research that requires skill for nanomaterials synthesis, solving the surface chemistry problems and colloidal stability issues, optimization of bioconjugation chemistry in preparing nanobioconjugates and their extensive in vitro and in vivo testing toward various biomedical applications. Current research efforts in this field include synthesis of high quality nanomaterials by greener approach,15 search for alternative non cadmium based quantum dot (QD),16 evaluating biocompatibility,17 minimization of nonspecific binding problem,18 development of various functionalization scheme in deriving nanobioconjugates, and exploring various bioaffinity molecules to improve labeling specificity and cellular trafficking mechanisms of nanoparticles.6 Nanoparticle-based probes have a high surface to volume ratio, and thus, a small change in particle size/shape or surface functional group can lead to significant alteration in cellular interaction. It is observed that cellular uptake, cytotoxicity, and subcellular localization of nanoparticle and QD is highly sensitive to particle size,19 shape,20 surface charge,21 and hydrophobicity.22 In addition, larger probe size (10-100 times compared to molecular probes) often leads to different endocytotic uptake mechanisms compared to molecular probes,23 induces high nonspecific cellular uptake of the nanoparticle * Corresponding author. E-mail:
[email protected].
probe,18 and often ends up at lysozome, preventing subcellular targeting.24 Thus researchers are focusing on the synthesis of responsive functional nanoparticles that would have endosomal escape/disruption property.25 Water-soluble functional nanomaterials are necessary for all biomedical applications.6-11 This is a particularly important issue because most of the powerful synthetic methods produce high quality nanoparticles which are capped with hydrophobic surfactants that are water insoluble and not functionalized.15,16,26-29 In addition nanoparticles have highly sensitive surface chemistry and they tend to grow or aggregate unless they are protected by the appropriate stabilizer. Thus it is necessary to develop various coating chemistry for different nanoparticle. The aim of these coatings is to convert hydrophobic nanoparticle into water-soluble nanoparticle, to stabilize the nanoparticle, and to introduce chemical functionality on the nanoparticle surface that would help to link the nanoparticle with various chemicals and biochemicals of interest.6 Functionalization is an important step that will assist labeling specificity of nanoprobes toward different applications. Most of the researchers employed surface adsorbed thiol molecules to stabilize and functionalize nanoparticles.3,5-9 However, the weak interaction between the stabilizer and nanoparticle surface often led to poor chemical, photochemical, and colloidal stability.30 Thus research efforts have been devoted to prepare core-shell type nanoparticles, similar to cross-linked block copolymer micelle.31 This type of shell could protect nanoparticles from adverse experimental conditions and provide better colloidal stability.6 It would be ideal to have a thin, cross-linked coating that could protect the core nanoparticle, improve colloidal stability, and introduce chemical functionality for bioconjugation. Our research focuses on synthesis of high quality nanomaterials,28,29,32-34 developing suitable surface coatings that can help in deriving various functional nanoparticle,35-51 and exploring various bioaffinity molecules to improve labeling specificity at cellular and subcellular length scales.45,46,48,49 In this review we will summarize our effort to develop different
10.1021/jp100844d 2010 American Chemical Society Published on Web 05/10/2010
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J. Phys. Chem. C, Vol. 114, No. 25, 2010
Nikhil R. Jana (born 1965) received his undergraduate degree (1987) from Midnapore College and his Masters (1989) and PhD (1994) from Indian Institute of Technology, Kharagpur, under the direction of Tarasankar Pal. He was a postdoctoral fellow at the University of South Carolina (1999-2001) in the laboratory of Catherine J. Murphy and at the University of Arkansas (2003) in the laboratory of Xiaogang Peng. He moved to Singapore in 2004 and worked as a Scientist at the Institute of Bioengineering and Nanotechnology, until he returned to India in 2008 and joined the Indian Association for the Cultivation of Science. His research interest includes advanced synthesis of nanomaterials, development of coating chemistry, and synthesis of functional nanoparticles and biomedical application of functional nanoparticles and quantum dots. Narayan Pradhan (born 1972) received his undergraduate (1992) and post graduate (1994) degrees from Utkal University, Bhubaneswar, and his Ph.D (2001) from Indian Institute of Technology, Kharagpur, under the supervision of Tarasankar Pal. He was a post doctoral fellow at the University of Negev, Beer-sheva, Israel in the laboratory of Shlomo Efrima (2001-2003) and at the University of Arkansas, Fayetteville (2003-2006) in the laboratory of Xiaogang Peng. He joined, as an Assistant Professor, the Department of Materials Science at Indian Association for the Cultivation of Science, Kolkata in 2007. He received LNJ Bhilwara Research Fellowship in 2007 which is named for LNJ Bhilwara of India. His research interest is the study of the physics and chemistry of colloidal dispersed nanoparticles. SK Basiruddin (born 1984) is a second year graduate student in Nikhil R. Jana’s group at the Indian Association for the Cultivation of Science. He obtained his undergraduate degree (2004) from Burdwan University and his Masters (2008) from Visva-Bharati University. His research interests include the development of coating chemistry and the synthesis of various functional nanoparticles. Arindam Saha (born 1984) is a second year graduate student in Nikhil R. Jana’s group at the Indian Association for the Cultivation of Science. He received his undergraduate degree (2006) from University of Calcutta and his Masters (2008) from Indian Institute of Technology, Kharagpur. His research interest includes synthesis of functional and hybrid nanoparticles with multifunctional properties.
coating chemistry in order to prepare a library of functional nanoparticles in the size range of 10-100 nm. In particular we will emphasize the importance of different cross-linked coatings, particularly the polyacrylate coating which provides a robust shell and opens the options for wide variety of functionalization.45-50 This feature article complements other recent articles, review articles, and feature articles.52-56 This article is composed of six sections besides the Introduction. Section 2 describes different types of nanoparticles depending on surface stabilizers and the importance of surface coatings. Section 3 discusses different coating approaches, their advantages and limitations. Section 4 highlights the preparation strategies of cross-linked coatings and their advantages in deriving functional nanoparticles. Section 5 describes the structural quality of cross-linked coatings. Section 6 summarizes emerging applications of nanoprobes with respect to cellular imaging and biomedical diagnostics. Section 7 outlines the limitations of existing crosslinked coatings with possible future directions. 2. Coating: Road toward Applications Nanoparticles can be divided into three types depending on the nature and design of the adsorbed coating molecules/ polymers as shown in Scheme 1. Among them surfactant- and polymer-coated hydrophilic nanoparticles (I) have been known for long time, hydrophobic nanoparticles with self-assembled surfactant monolayer structures (II) have been extensively studied for the last 20 years, and core-shell type hydrophilic nanoparticles with cross-linked shells (III) are a recent focus. However, most of these as synthesized nanoparticles, particularly types I and II, can not be used directly for applications as they are either water insoluble or not functionalized. Water-soluble nanoparticles of type I are mostly capped with loosely bound molecules and have poor colloidal stability. Thus further
Basiruddin et al. SCHEME 1: Structures of Three Types of Nanoparticles with Different Coatingsa
a I: surfactant/polymer coated hydrophilic nanoparticles, II: hydrophobic nanoparticles with self-assembled surfactant monolayer, III: core-shell type hydrophilic nanoparticles with cross-linked shells structure.
stabilization and functionalization steps are necessary prior to their applications. Type II nanoparticles are most widely studied currently as they are highly monodispersed, but they have hydrophobic surfactants capping that render them water insoluble. Thus they need to be transformed into water-soluble nanoparticles, and more importantly, they have to be linked with different affinity molecules in order to ensure the labeling specificity. This step can be performed either by replacing the capping molecules of the as synthesized nanoparticles with affinity molecules or by linking the capping molecule with the affinity molecules. These steps are associated with different conjugation chemistries and chromatographic purification steps and often nanoparticles aggregate or precipitate due to weakly adsorbed molecules. In order to overcome these limitations, researchers are becoming more and more interested into the nanoparticles of types III, having hydrophilic robust shells that not only protect nanoparticles from adverse physical and chemical environment but also give the options to prepare various functional nanoparticles. Development of type III nanoparticles from as synthesized nanoparticles involves various coating chemistry as shown in Schemes 2 and 3. In this coating step, adsorbed molecules present in the as synthesized nanoparticles are completely or partially replaced by new molecules/polymers. This step increases the water solubility and colloidal stability of nanoparticles and introduces the chemical functionality for conjugation chemistry. In next two sections, we will discuss various coating strategies with the emphasis on robust coating. 3. Different Coating Approaches: Success and Limitations Ligand exchange approaches are the most widely used coating methods for the wide range of nanoparticles of type II. In this method hydrophobic surfactant molecules are completely or partially replaced by another small molecule or polymer. Details of different types of ligand exchange methods are summarized in Scheme 2. The most popular method is to exchange with small thiolated molecules such as dodecanethiol, mercaptopropionic acid, mercaptoundecanoic acid, and cysteine, shown as ligand exchange type 1 (LE-1).28,30,37,57-59 This method is based on the chemical affinity of thiol groups to the nanoparticles and thus most effective to noble metal nanoparticles. In order to increase the ligand binding affinity and to extend to other nanoparticles, different bidentate and polydentate molecules/ polymers are used which is shown as ligand exchange type 2 (LE-2).35,38,60-64 The molecules used in this method include dimercaptosuccinic acid,60 lipoic acid and its derivatives,61-64 and polydentate thiols such as cysteine functionalized polyas-
Feature Article
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SCHEME 2: Various Ligand Exchange (LE) Based Coating Strategy Used for Type II Nanoparticles and Their Conversion Steps into Nanoparticles of Type IIIa
a LE-1 involves monodentate thiols such as mercaptopropionic acid whereas LE-2 involves bidentate or polydentate thiols such as dimercaptosuccinic acid or cysteine functionalized polyaspartic acid. LE-3 and LE-4 involve partial ligand exchange where lipid like small molecules are used in LE-3 and polymers having multiple anchoring hydrocarbon chains are used in LE-4. A ligand bridging step can be employed further for some of these ligand exchanged nanoparticles to cross-link the shell structure.
partic acid38 or thiolated chitosan.35 We have shown that multiple thiols/amines/acids groups in a polymer backbone acts as a more effective capping agent than monodentate ligands and the ligand exchange method can be extended to quantum dot, iron oxide in addition to noble metal nanoparticles.38,50 This ligand exchange approach is particularly useful in making water-soluble nanoparticles of small hydrodynamic diameter (
